Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1639 | 5140;5141;5142 | chr2:178776949;178776948;178776947 | chr2:179641676;179641675;179641674 |
| N2AB | 1639 | 5140;5141;5142 | chr2:178776949;178776948;178776947 | chr2:179641676;179641675;179641674 |
| N2A | 1639 | 5140;5141;5142 | chr2:178776949;178776948;178776947 | chr2:179641676;179641675;179641674 |
| N2B | 1593 | 5002;5003;5004 | chr2:178776949;178776948;178776947 | chr2:179641676;179641675;179641674 |
| Novex-1 | 1593 | 5002;5003;5004 | chr2:178776949;178776948;178776947 | chr2:179641676;179641675;179641674 |
| Novex-2 | 1593 | 5002;5003;5004 | chr2:178776949;178776948;178776947 | chr2:179641676;179641675;179641674 |
| Novex-3 | 1639 | 5140;5141;5142 | chr2:178776949;178776948;178776947 | chr2:179641676;179641675;179641674 |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 1.0 | D | 0.765 | 0.726 | 0.480647642424 | gnomAD-4.0.0 | 1.59118E-06 | None | None | None | None | I | None | 0 | 2.28802E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs760219634  |
0.428 | 1.0 | N | 0.871 | 0.714 | 0.575180444326 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs760219634 |
0.428 | 1.0 | N | 0.871 | 0.714 | 0.575180444326 | gnomAD-4.0.0 | 1.59118E-06 | None | None | None | None | I | None | 0 | 2.28802E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7375 | likely_pathogenic | 0.7185 | pathogenic | -0.583 | Destabilizing | 1.0 | D | 0.813 | deleterious | N | 0.496188431 | None | None | I |
| D/C | 0.9773 | likely_pathogenic | 0.9683 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| D/E | 0.7268 | likely_pathogenic | 0.675 | pathogenic | -0.791 | Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.508630277 | None | None | I |
| D/F | 0.9793 | likely_pathogenic | 0.9739 | pathogenic | -0.184 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| D/G | 0.8162 | likely_pathogenic | 0.7674 | pathogenic | -0.941 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.616708717 | None | None | I |
| D/H | 0.947 | likely_pathogenic | 0.9362 | pathogenic | -0.504 | Destabilizing | 1.0 | D | 0.763 | deleterious | D | 0.640926427 | None | None | I |
| D/I | 0.971 | likely_pathogenic | 0.9626 | pathogenic | 0.363 | Stabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | I |
| D/K | 0.9826 | likely_pathogenic | 0.9783 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| D/L | 0.9681 | likely_pathogenic | 0.9593 | pathogenic | 0.363 | Stabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | I |
| D/M | 0.9867 | likely_pathogenic | 0.9816 | pathogenic | 0.785 | Stabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| D/N | 0.5563 | ambiguous | 0.4881 | ambiguous | -0.914 | Destabilizing | 1.0 | D | 0.667 | neutral | D | 0.564675537 | None | None | I |
| D/P | 0.9994 | likely_pathogenic | 0.9989 | pathogenic | 0.073 | Stabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| D/Q | 0.9539 | likely_pathogenic | 0.9443 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| D/R | 0.9826 | likely_pathogenic | 0.9796 | pathogenic | -0.315 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | I |
| D/S | 0.6216 | likely_pathogenic | 0.5855 | pathogenic | -1.188 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/T | 0.8893 | likely_pathogenic | 0.8647 | pathogenic | -0.901 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| D/V | 0.8918 | likely_pathogenic | 0.8714 | pathogenic | 0.073 | Stabilizing | 1.0 | D | 0.871 | deleterious | N | 0.502981042 | None | None | I |
| D/W | 0.9978 | likely_pathogenic | 0.9971 | pathogenic | -0.017 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| D/Y | 0.91 | likely_pathogenic | 0.8897 | pathogenic | 0.051 | Stabilizing | 1.0 | D | 0.85 | deleterious | D | 0.641585319 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.